Quinolone antibiotics - limit use

Quinolones are associated with increasing antimicrobial resistance. Their use needs to be reserved for specific indications involving serious bacterial infections, in order to protect their effectiveness. There are very few situations in general practice where a quinolone would be considered first-line treatment. Ciprofloxacin may be considered for the treatment of patients with pyelonephritis, travellers’ diarrhoea, gonorrhoea (if sensitive) and severe cases of salmonellosis. Norfloxacin may be considered as a second-line treatment for urinary tract infection if other antibiotic treatment has failed or is not suitable.

Key concepts

There are very few situations in general practice where quinolones are considered first line treatment

Ciprofloxacin may be used for acute pyelonephritis, severe travellers’ diarrhoea, severe cases of salmonellosis
and for gonorrhoea (if known to be sensitive)

Ciprofloxacin should not be used in pneumococcal pneumonia as it does not cover Streptococcus pneumoniae adequately

Norfloxacin can be considered as a second-line treatment in urinary tract infections, if other antibiotic treatment
has failed or is not suitable

Elderly people are at increased risk of experiencing adverse effects to quinolones. Adverse effects of the central
nervous system, such as anxiety, restlessness and insomnia, are of particular concern

Rare but serious adverse effects of quinolones include tendinitis, QT prolongation and photosensitivity

There are few indications for quinolones in General Practice

Fluoroquinolones (commonly referred to as quinolones) are a class of broad-spectrum antibiotics, often implicated in
antimicrobial resistance. Quinolones available in New Zealand include:

Ciprofloxacin (tablets and eye drops)

Norfloxacin

Moxifloxacin (specialist use only)

Indications in general practice

Quinolones should be reserved for serious bacterial infections, and used only when there is no practical alternative.

There are very few situations in general practice where a quinolone would be considered first-line treatment. Ciprofloxacin
may be considered for the treatment of patients with pyelonephritis, travellers’ diarrhoea, gonorrhoea (if sensitive)
and severe cases of salmonella. Norfloxacin may be considered as a second-line option (after trimethoprim or nitrofurantoin)
for recurrent UTI or for people who have failed to respond to a first-line antibiotic treatment for UTI. N.B. quinolones
should not be used in pregnant women.

Pharmaceutical dispensing data in New Zealand indicates that the use of ciprofloxacin is continuing to increase, along
with consistently high levels of norfloxacin. This is of concern as community prescribing of quinolones significantly
contributes to antimicrobial resistance.

Ciprofloxacin should be used only when there is no alternative1,2,3,4,5

Salmonellosis – antibiotics are not routinely required therefore only use for invasive or severe infection and in
immunocompromised patients.

Other indications include acute prostatitis, invasive pseudomonas infections, bone and joint infections and prophylaxis
of meningococcal disease, when no alternative is available.

Antibiotics are not routinely required for campylobacteriosis, but ciprofloxacin can be considered second-line
if treatment with erythromycin has failed.

Inappropriate use

Should not be used for pneumococcal pneumonia.

Repeated courses should be avoided in chronic prostatitis if bacterial involvement has not been confirmed, as chronic
prostate pain is frequently not due to infection.

Contraindicated during pregnancy and lactation.

Norfloxacin is a second-line treatment for urinary tract infections1,2,3,6

Spectrum

Mainly active against Gram-negative pathogens

Resistance

Urinary isolates of E. coli resistant to quinolones have increased from 1.9% in 2002 to
7.7% in 2009. This varies with geographical location.

Uses in general practice

Norfloxacin may be considered for the treatment of urinary tract infections (UTI) in recurrent
infections or where treatment with a first-line antibiotic has failed.

Inappropriate use

Not recommended as first-line treatment for urinary tract infections.

It is not appropriate to use norfloxacin for upper urinary tract infections including pyelonephritis.

Contraindicated during pregnancy and lactation.

Comments

Some DHBs have excluded norfloxacin from their formularies as it is no longer considered appropriate.

Ciprofloxacin is more appropriate to use than norfloxacin if there is any suggestion of upper urinary tract involvement.

The most appropriate antibiotic for the empiric treatment of uncomplicated UTI is either nitrofurantoin
or trimethoprim.

Moxifloxacin is for specialist use only1,3,4,7

Spectrum

Improved activity against Gram-positive and atypical pathogens, as well as anaerobes.

Enterococci are likely to be intrinsically resistant.

Resistance

Moxifloxacin is a newer quinolone, developed due to resistance associated with other quinonlones.
There is no current data on resistance.

Use

Many drug resistant Streptococcus pneumoniae isolates are susceptible to moxifloxacin.

Comments

Special authority criteria apply.

QT interval prolongation may be more of a concern than with other commonly used quinolones.

Moxifloxacin should not be considered active against Pseudomonas aeruginosa or methicillin-resistant Staphylococcus
aureus.

Adverse effects associated with quinolones

Common adverse effects include dyspepsia, dizziness and rash

The most common adverse effects associated with quinolones include gastrointestinal and central nervous system (CNS)
toxicity such as nausea, diarrhoea, abdominal pain, dyspepsia, dizziness, headache and insomnia. Rash is also a common
adverse effect. Rare but clinically important adverse effects include QT interval prolongation, tendinitis and tendon
rupture (see below), disrupted glucose metabolism, seizures and photosensitivity.3,7

Patients should be well informed so that they can prevent or minimise the impact of any adverse effects if they occur.

Advise patients to:

Increase fluid intake to reduce the risk of crystalluria

Apply sunscreen when outdoors to avoid a photosensitivity reaction

Cease taking the quinolone if tendon pain or swelling occurs

Use quinolones with caution in older people and people with epilepsy

Many of the adverse effects associated with quinolones occur more frequently in people with pre-existing risk factors,
or in certain at risk groups, including older people and those with epilepsy.

Older people

Quinolones should be used at the lowest effective dose in older people. Renal function declines consistently with age
and quinolone doses need to be reduced accordingly to avoid adverse effects. For example, an appropriate dose for ciprofloxacin
in renal impairment is 250–500 mg, twice daily, if eGFR is 30–60 mL/minute/1.73 m2 or once daily, if eGFR is
less than 30 mL/minute/1.73 m2.4

Adverse CNS effects are of particular concern in older people and may include anxiety, restlessness, nervousness, confusion,
weakness, insomnia, euphoria, nightmares, hallucinations, psychosis and seizures.3 Some of these signs and
symptoms may be attributed to “old age”, so it is important to consider quinolone use when such symptoms are
reported.3 Factors that increase the risk of these adverse effects include the dose not being reduced in renal
insufficiency, electrolyte imbalance and a history of seizures.3

People with epilepsy or a history of CNS disorders

As CNS effects may occur with quinolone use, they should be used with caution in people at increased risk of seizures,
with CNS disorders or in those concurrently using medicines which may lower the seizure threshold, e.g. bupropion. The
potential for seizures, although very rare, may be increased with concomitant NSAID treatment.3,4

Quinolones are most active against Gram-negative bacteria

Quinolones are very active against aerobic Gram-negative bacilli and cocci including Enterobacteriaceae, Haemophilus
influenzae, Moraxella catarrhalis (Branhamella catarrhalis) and Neisseria gonorrhoeae and are also active
against Pseudomonas aeruginosa. They are generally less active against Gram-positive organisms such as staphylococci
and much less active against streptococci such as Streptococcus pneumoniae.1 Quinolones are not
effective against anaerobic organisms.

Other at risk groups

Care is also required with quinolone use in people with:4

Diabetes - glucose levels may be altered

Myasthenia gravis – symptoms may be exacerbated

G6PD deficiency – increased risk of haemolytic anaemia

Quinolones are generally not used in children

Quinolones are not recommended for use in children and adolescents aged under 18 years as they are associated with adverse
effects on cartilage and tendons.3 There are some specific circumstances, such as pseudomonal infections associated
with cystic fibrosis, where the short term use of ciprofloxacin may be justified in children.4

Tendinitis and tendon ruptures are a rare adverse effect

A number of toxicological studies have confirmed that quinolones damage cartilage fibres, which on rare occasions can
result in tenditinits and tendon rupture. This can occur even after a single dose of quinolone and the effect can persist
for months.3,7 Tendon rupture has been reported within 48 hours of starting treatment, however, cases have
also been reported several months after stopping treatment.

The risk of tendonopathy is increased in people aged over 60 years, people using long-term corticosteroid treatment
and people with chronic kidney disease.3

Although this adverse effect is rare (estimated incidence rate 0.14% to 0.4%),7 it is important to remember
that:4

Quinolones are contraindicated in patients with a history of tendon disorders related to previous quinolone use

If tendinitis is suspected, the quinolone should be discontinued immediately.

The future for quinolones

Despite increasing resistance and adverse effects, quinolones are still an important antimicrobial medicine. Research
and development goals include identifying new quinolones with expanded coverage to bacterial pathogens such as MRSA and
multi drug resistant tuberculosis, as well as improved pharmacokinetic and safety profiles.1

A restrictive approach to the use of quinolones is recommended. Ideally they should be reserved for serious, life-threatening
or difficult-to-treat infections, when other antibiotics cannot be used due to allergy or intolerance, or when the pathogen
is resistant to alternative antimicrobial agents.

Increasing resistance to quinolones is concerning

Antimicrobial resistance to quinolones is prevalent in many geographic locations in New Zealand, and includes both
Gram-negative and Gram-positive strains.1

Acute uncomplicated cystitis is one of the most common indications for prescribing antibiotics in otherwise healthy
women.6 Antimicrobial resistance to uropathogens causing uncomplicated cystitis has increased over time.4

Uncomplicated cystitis and pyelonephritis is mainly caused by E. coli (75 to 95%), with occasional involvement
of Enterobacteriaceae, such as Proteus mirabilis and Klebsiella pneumoniae, and Staphylococcus
saprophyticus. Local antimicrobial susceptibility patterns of E. coli should be considered in empirical
antibiotic selection.6

While quinolones are an effective treatment for acute cystitis, the pattern of increasing antimicrobial resistance
threatens their long-term usefulness. The resistance level of urinary E. coli infections to quinolones is approaching
8% (Table 1).2 There is also concern about the association between quinolone use and increased rates of MRSA
infections.6

Although local antimicrobial resistance rates are often skewed by data obtained from infections treated in the hospital
setting, which are more likely to be complicated infections, quinolone resistance is also linked to community prescribing
practices and therefore restrictive use is important.

Gonorrhoea – ciprofloxacin resistance greater than for penicillin

Penicillin was originally used to treat gonorrhoea but increasing penicillin resistance meant that empiric treatment
with ciprofloxacin became more favoured. Data collected by ESR in 2009 reveals that resistance levels of N. Gonorrhoeae to
quinolones is approaching 30%.2 This far exceeds the acceptable 5% resistance threshold for first-line therapy.
The rate of penicillin resistance for the same time period was approximately 12%.2 Ciprofloxacin resistance
is now more prevalent than penicillin resistance in most areas of New Zealand, but local variations do occur. Ceftriaxone
injection is advised for treating suspected gonorrhoea, unless susceptibility data is available.

Gupta K, Hooton TM, Naber KG, et al. International clinical practice guidelines for the treatment of acute uncomplicated
cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society
for Microbiology and Infectious Diseases. Clin Infect Dis 2011;52(5):e103–e120.